tbuckley/cabot-search huggingface dataset:
PB2641: THROMBOELASTOGRAPHY (TEG) REFERENCE RANGES IN A HEALTHY PAEDIATRIC COHORT SHOW ACCELERATED COAGULATION AND CLOT FORMATION TIME.
Authors: Irene Regan, Dermot Cox, Colin Mcmahon
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: “Developmental hemostasis” refers to the dynamic process of gradual hemostatic maturation. Conventional coagulation tests seem to fail to accurately depict the in vivo hemostasis, while viscoelastic tests appear very promising as they provide insight more rapidly and accurately into the hemostatic potential. Aims: As part of a larger study we derived a reference range (RR) for children using thromboelastography (TEG) and compared it with an adult range recruited at the same time. Methods: Citrated native TEG assays were run at 37°C using a two- channel thromboelastograph (TEG 5000 Hemoscope; Haemonetics, Niles, Illinois, USA), by adding 20 µL of 0.2 mol/L CaCl2 followed by citrated blood into the warmed TEG cup. We collected the following parameters: Reaction time (R): time (minutes) to initial clot formation (2 mm). Kinetics (K): time (minutes) to significant clot strength (20 mm) Alpha angle (α): angle (°) between the midline and the tangent to the trace. Maximum amplitude (MA): widest trace amplitude (millimetres) representing maximum clot strength Results: We showed that children up to 1 year have accelerated coagulation and clot formation time compared to older children and adults. The shorter coagulation time in infants might be attributed to the increased levels of procoagulant factors, such as fibrinogen, factor V, factor VIII, and von Willebrand factor (vWF) as compared to adults.Summary/Conclusion: This study findings start to address the issue of quality, in providing paediatric values for TEG,which are different from manufacturer recommended values generated from adults. We observed significant differences according to age, emphasising the importance of paediatric RRs. Although there is no evidence of an increased tendency toward bleeding or thrombosis, age-related differences in coagulation parameters have been consistently reported in healthy children, particularly in the first year of life. Keywords: Thrombelastograph, Coagulation, Children
Preserved respiratory chain capacity and physiology in mice with profoundly reduced levels of mitochondrial respirasomes
Authors: Dusanka Milenkovic, Jelena Misic, Johannes F. Hevler, Thibaut Molinié, Injae Chung, Ilian Atanassov, Xinping Li, Roberta Filograna, Andrea Mesaros, Arnaud Mourier, Albert J.R. Heck, Judy Hirst, Nils-Göran Larsson
Journal: Cell Metabolism (2023)

The mammalian respiratory chain complexes I, III
A phase I, first-in-human study to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of MRG-001 in healthy subjects
Authors: Ali R. Ahmadi, George Atiee, Bart Chapman, Laurie Reynolds, John Sun, Andrew M. Cameron, Russell N. Wesson, James F. Burdick, Zhaoli Sun
Journal: Cell Reports Medicine (2023)

Preclinical studies demonstrate that pharmacological mobilization and recruitment of endogenous bone marrow stem cells and immunoregulatory cells by a fixed-dose drug combination (MRG-001) improves wound healing, promotes tissue regeneration, and prevents allograft rejection. In this phase I, first-in-human study, three cohorts receive subcutaneous MRG-001 or placebo, every other day for 5 days. The primary outcome is safety and tolerability of MRG-001. Fourteen subjects received MRG-001 and seven received a placebo. MRG-001 is safe over the selected dose range. There are no clinically significant laboratory changes. The intermediate dose group demonstrates the most significant white blood cell, stem cell, and immunoregulatory cell mobilization. PBMC RNA sequencing and gene set enrichment analysis reveal 31 down-regulated pathways in the intermediate MRG-001 dose group compared with no changes in the placebo group. MRG-001 is safe across all dose ranges. MRG-001 may be a clinically useful therapy for immunoregulation and tissue regeneration (ClinicalTrials.gov: NCT04646603).
Plasma proteomic profiling discovers molecular features associated with upper tract urothelial carcinoma
Authors: Yuanyuan Qu, Zhenmei Yao, Ning Xu, Guohai Shi, Jiaqi Su, Shiqi Ye, Kun Chang, Kai Li, Yunzhi Wang, Subei Tan, Xiaoru Pei, Yijiao Chen, Zhaoyu Qin, Jinwen Feng, Jiacheng Lv, Jiajun Zhu, Fahan Ma, Shaoshuai Tang, Wenhao Xu, Xi Tian, Aihetaimujiang Anwaier, Sha Tian, Wenbo Xu, Xinqiang Wu, Shuxuan Zhu, Yu Zhu, Dalong Cao, Menghong Sun, Hualei Gan, Jianyuan Zhao, Hailiang Zhang, Dingwei Ye, Chen Ding
Journal: Cell Reports Medicine (2023)

Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Limited data are available on potential non-invasive biomarkers for disease monitoring. Here, we investigate the proteomic profile of plasma in 362 UTUC patients and 239 healthy controls. We present an integrated tissue-plasma proteomic approach to infer the signature proteins for identifying patients with muscle-invasive UTUC. We discover a protein panel that reflects lymph node metastasis, which is of interest in identifying UTUC patients with high risk and poor prognosis. We also identify a ten-protein classifier and establish a progression clock predicting progression-free survival of UTUC patients. Finally, we further validate the signature proteins by parallel reaction monitoring assay in an independent cohort. Collectively, this study portrays the plasma proteomic landscape of a UTUC cohort and provides a valuable resource for further biological and diagnostic research in UTUC.
Multi-cell type and multi-level graph aggregation network for cancer grading in pathology images
Authors: Syed Farhan Abbas, Trinh Thi Le Vuong, Kyungeun Kim, Boram Song, Jin Tae Kwak
Journal: Medical Image Analysis (2023)

In pathology, cancer grading is crucial for patient management and treatment. Recent deep learning methods, based upon convolutional neural networks (CNNs), have shown great potential for automated and accurate cancer diagnosis. However, these do not explicitly utilize tissue/cellular composition, and thus difficult to incorporate the existing knowledge of cancer pathology. In this study, we propose a multi-cell type and multi-level graph aggregation network (MMGA-Net) for cancer grading. Given a pathology image, MMGA-Net constructs multiple cell graphs at multiple levels to represent intra- and inter-cell type relationships and to incorporate global and local cell-to-cell interactions. In addition, it extracts tissue contextual information using a CNN. Then, the tissue and cellular information are fused to predict a cancer grade. The experimental results on two types of cancer datasets demonstrate the effectiveness of MMGA-Net, outperforming other competing models. The results also suggest that the information fusion of multiple cell types and multiple levels via graphs is critical for improved pathology image analysis.
The respiratory tract microbiome, the pathogen load, and clinical interventions define severity of bacterial pneumonia
Authors: Ana Elena Pérez-Cobas, Christophe Ginevra, Christophe Rusniok, Sophie Jarraud, Carmen Buchrieser
Journal: Cell Reports Medicine (2023)

Bacterial pneumonia is a considerable problem worldwide. Here, we follow the inter-kingdom respiratory tract microbiome (RTM) of a unique cohort of 38 hospitalized patients (n = 97 samples) with pneumonia caused by Legionella pneumophila. The RTM composition is characterized by diversity drops early in hospitalization and ecological species replacement. RTMs with the highest bacterial and fungal loads show low diversity and pathogen enrichment, suggesting high biomass as a biomarker for secondary and/or co-infections. The RTM structure is defined by a "commensal" cluster associated with a healthy RTM and a "pathogen" enriched one, suggesting that the cluster equilibrium drives the microbiome to recovery or dysbiosis. Legionella biomass correlates with disease severity and co-morbidities, while clinical interventions influence the RTM dynamics. Fungi, archaea, and protozoa seem to contribute to progress of pneumonia. Thus, the interplay of the RTM equilibrium, the pathogen load dynamics, and clinical interventions play a critical role in patient recovery.
Vascular cognitive impairment – Past, present, and future challenges
Authors: Atef Badji, Jessica Youwakim, Alexandra Cooper, Eric Westman, Anna Marseglia
Journal: Ageing Research Reviews (2023)

Vascular cognitive impairment (VCI) is a lifelong process encompassing a broad spectrum of cognitive disorders, ranging from subtle or mild deficits to prodromal and fully developed dementia, originating from cerebrovascular lesions such as large and small vessel disease. Genetic predisposition and environmental exposure to risk factors such as unhealthy lifestyles, hypertension, cardiovascular disease, and metabolic disorders will synergistically interact, yielding biochemical and structural brain changes, ultimately culminating in VCI. However, little is known about the pathological processes underlying VCI and the temporal dynamics between risk factors and disease mechanisms (biochemical and structural brain changes). This narrative review aims to provide an evidence-based summary of the link between individual vascular risk/disorders and cognitive dysfunction and the potential structural and biochemical pathophysiological processes. We also discuss some key challenges for future research on VCI. There is a need to shift from individual risk factors/disorders to comorbid vascular burden, identifying and integrating imaging and fluid biomarkers, implementing a life-course approach, considering possible neuroprotective influences of positive life exposures, and addressing biological sex at birth and gender differences. Finally, this review highlights the need for future researchers to leverage and integrate multidimensional data to advance our understanding of the mechanisms and pathophysiology of VCI.
Genome-Wide Meta-analysis Identifies Risk Loci and Improves Disease Prediction of Age-Related Macular Degeneration
Authors: Weixiong He, Xikun Han, Jue-Sheng Ong, Yeda Wu, Alex W. Hewitt, David A. Mackey, Puya Gharahkhani, Stuart MacGregor
Journal: Ophthalmology (2023)

To identify age-related macular degeneration (AMD) risk loci and to establish a polygenic prediction model.Genome-wide association study (GWAS) and polygenic risk score (PRS) construction.We included 64 885 European patients with AMD and 568 740 control participants (with overlapped samples) in the UK Biobank, Genetic Epidemiology Research on Aging (GERA), International AMD Consortium, FinnGen, and published early AMD GWASs in meta-analyses, as well as 733 European patients with AMD and 20 487 control participants from the Canadian Longitudinal Study on Aging (CLSA) and non-Europeans from the UK Biobank and GERA for polygenic risk score validation.A multitrait meta-analysis of GWASs comprised 64 885 patients with AMD and 568 740 control participants; the multitrait approach accounted for sample overlap. We constructed a PRS for AMD based on both previously reported as well as unreported AMD loci. We applied the PRS to nonoverlapping data from the CLSA.We identified several single nucleotide polymorphisms associated with AMD and established a PRS for AMD risk prediction.We identified 63 AMD risk loci alongside the well-established AMD loci CFH and ARMS2, including 9 loci that were not reported in previous GWASs, some of which previously were linked to other eye diseases such as glaucoma (e.g., HIC1). We applied our PRS to nonoverlapping data from the CLSA. A new PRS was constructed using the PRS method, PRS-CS, and significantly improved the prediction accuracy of AMD risk compared with PRSs from previously published datasets. We further showed that even people who carry all the well-known AMD risk alleles at CFH and ARMS2 vary considerably in their AMD risk (ranging from close to 0 in individuals with low PRS to > 50% in individuals with high PRS). Although our PRS was derived in individuals of European ancestry, the PRS shows potential for predicting risk in people of East Asian, South Asian, and Latino ancestry.Our findings improve the knowledge of the genetic architecture of AMD and help achieve better accuracy in AMD prediction.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector (VSVMT) in golden syrian hamster
Authors: Yong Ke, En Zhang, Jianming Guo, Xiaoxiao Zhang, Lei Wang, Duo Chen, Xinkui Fang, Jianwei Zhu, Feng Li, Tao Sun, Baohong Zhang
Journal: Acta Pharmaceutica Sinica B (2023)

COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.
The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Proposal for the T Component for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors
Authors: Meinoshin Okumura, Mirella Marino, Vanessa Cilento, Emily Goren, Enrico Ruffini, Daniel Dibaba, Usman Ahmad, Sarit Appel, Andrea Bille, Souheil Boubia, Cecilia Brambilla, Ayten Kayi Cangir, Frank Detterbeck, Conrad Falkson, Wentao Fang, Pier Luigi Filosso, Giuseppe Giaccone, Nicolas Girard, Francesco Guerrera, James Huang, Maurizio Infante, Dong Kwan Kim, Marco Lucchi, Edith M. Marom, Andrew G. Nicholson, Ramon Rami-Porta, Andreas Rimner, Charles B. Simone, Hisao Asamura
Journal: Journal of Thoracic Oncology (2023)
Competency-based cardiac imaging for patient-centred care. A statement of the European Society of Cardiology (ESC). With the contribution of the European Association of Cardiovascular Imaging (EACVI), and the support of the Association of Cardiovascular Nursing &amp; Allied Professions (ACNAP), the Association for Acute CardioVascular Care (ACVC), the European Association of Preventive Cardiology (EAPC), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European…
Authors: Mark Westwood, Ana G Almeida, Emanuele Barbato, Victoria Delgado, Santo Dellegrottaglie, Kevin F Fox, Luna Gargani, Kurt Huber, Pál Maurovich-Horvat, Jose L Merino, Richard Mindham, Denisa Muraru, Lis Neubeck, Robin Nijveldt, Michael Papadakis, Gianluca Pontone, Susanna Price, Giuseppe M C Rosano, Alexia Rossi, Leyla Elif Sade, Jeanette Schulz-Menger, Franz Weidinger, Stephan Achenbach, Steffen E Petersen
Journal:  (2023)

Abstract Imaging plays an integral role in all aspects of managing heart disease and cardiac imaging is a core competency of cardiologists. The adequate delivery of cardiac imaging services requires expertise in both imaging methodology—with specific adaptations to imaging of the heart—as well as intricate knowledge of heart disease. The European Society of Cardiology (ESC) and the European Association of Cardiovascular Imaging have developed and implemented a successful education and certification programme for all cardiac imaging modalities. This programme equips cardiologists to provide high quality competency-based cardiac imaging services ensuring they are adequately trained and competent in the entire process of cardiac imaging, from the clinical indication via selecting the best imaging test to answer the clinical question, to image acquisition, analysis, interpretation, storage, repository, and results dissemination. This statement emphasizes the need for competency-based cardiac imaging delivery which is key to optimal, effective and efficient, patient care.
PB1952: CLL IN AYA
Authors: Shehab Mohamed, Dina Soliman, Ruba Taha, Hesham Elsabah, Awni Alshurafa, Amna Gamil, Mohamed Yassin, Firyal Ibrahim
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Chronic lymphocytic leukemia (CLL) is a monoclonal disorder characterized by a progressive proliferation of dysfunctional mature lymphocytes. Its disease of elderly with average age at presentation 70 years old. AYA cancer patients are defined as those patients’ ages between 15-39 years according to NCCN guidelines. CLL in AYA are less than 1% of the cases. However due to lack of enough data more knowledge and experience is needed Aims: To describe young and adolescence diagnosed with CLL in tertiary cancer hospital Methods: We retrospectively analyzed data from the clinical database of our single tertiary hematology center, The National Center for Cancer Care and Research, Doha, Qatar. All patients diagnosed with CLL during the period of January 2012 to December 2021 where included less than 40 years from (15-39) Results: Four patients out of 140 patients diagnosed with CLL in our center and their age below 40. Male and females were equal, two patients at 32 years and another two at 37. On presentation median WBC 290,000 with lymphocytosis of 56000, while median hemoglobin 7.8 and 14000 for platelets. Two patients had B symptoms, while other two incidental findings. All the patients have cervical lymphadenopathy plus or minus adenopathy in other areas. Advanced stage IV in three patients. Karyotype were different with one patient has diploid, trisomy 12, del 13q and the last patient with complex karyotype. A least one or two of the poor prognostic finding or markers were in each patient. The poor markers were CD49, atypical CD79, and CD38, extensive bone marrow infiltration, advance stage, complex karyotype or tp53. Treatments were the most challenging part within young group. One patient got pregnant while on BTKi so we have to hold, as consequence WBC has increase and lymph node were enlarged. she is for early-planed delivery so we can resume later her treatment. Another patient who received FCR 6 cycles developed PML as complications to rituximab. Third patient declined treatment not wiling for chemotherapy neither for lifelong treatment Summary/Conclusion: Although it is rare, CLL in young adult seems to be quite challenging due to negative prognostic markers for this group and for other problems withs treatment options. Childbearing age is among this group with no evident treatment options or guidelines for management. Long term complications are an issue to consider with fixed duration treatment such as Venetoclax based or other regimens. Keywords: B-CLL
PB2709: BURDEN OF SEVERE INFECTIONS IN PRIMARY IMMUNODEFICIENCY DISEASES
Authors: Saurabh Aggarwal, Ozlem Topaloglu, Sushil Kumar
Journal: HemaSphere (2023)

Topic: 36. Ethics and health economics Background: Primary immunodeficiencies (PI) are a diverse group of genetic aberrations of the immune system that result in an increased risk of recurrent bacterial and viral infections. There is a lack of evidence on trends in incidence and burden of severe infections in PI patients. Aims: To assess the burden of severe infections in patients with Primary Immunodeficiency (PI) diseases Methods: The 2016 National Inpatient Sample (NIS) data set from the Healthcare Cost and Utilization Project was utilized in order to analyze hospital admission records for patients with PI. All severe infections were coded based on a targeted review of the literature. Two cohorts of patients were designed: PI with severe infection and w/o severe infection. Thirty comorbidities were assessed using Elixhauser scoring. Multivariate logistic regression was conducted to assess predictor variables for LOS and costs. Results: In 2016, there were an estimated 114,100 hospitalizations with a diagnosis of PI, 44% with severe infections and 56% without severe infections. Demographically two cohorts are similar in terms of age, gender, race and insurance (53.73 [SD 23.02] vs 48.03 [SD 25.3] years old; Male 49% vs 46%, Medicare 49% vs 42%, White 75% vs 71%, Comorbidity score 3.9 vs 3.5, with vs without severe infections respectively). The hospital length of stay was longer in patients with severe infections (Mean 9.97 vs 8.01, p<0.05, Median 6 vs 4 days). The mean hospital charges in PI with severe infections vs without groups were $122,739 and $103,859, p<0.05, respectively. The mortality rate was significantly higher in the severe group 6.77% vs 2.09%, p<0.05. Two most common infections were pneumonia (J189) and Enterocolitis due to Clostridium difficile (A047). The top non-PI ICD-10 code in the severe infection group was sepsis, while in the non-infection group it was Encounter for chemotherapy. Summary/Conclusion: Analysis of hospital records shows primary Immunodeficiency patients with severe infections incur significant costs, high morbidity and mortality. Keywords: Immunodeficiency
Learning functional conservation between human and pig to decipher evolutionary mechanisms underlying gene expression and complex traits
Authors: Jinghui Li, Tianjing Zhao, Dailu Guan, Zhangyuan Pan, Zhonghao Bai, Jinyan Teng, Zhe Zhang, Zhili Zheng, Jian Zeng, Huaijun Zhou, Lingzhao Fang, Hao Cheng
Journal: Cell Genomics (2023)

Assessment of genomic conservation between humans and pigs at the functional level can improve the potential of pigs as a human biomedical model. To address this, we developed a deep learning-based approach to learn the genomic conservation at the functional level (DeepGCF) between species by integrating 386 and 374 functional profiles from humans and pigs, respectively. DeepGCF demonstrated better prediction performance compared with the previous method. In addition, the resulting DeepGCF score captures the functional conservation between humans and pigs by examining chromatin states, sequence ontologies, and regulatory variants. We identified a core set of genomic regions as functionally conserved that plays key roles in gene regulation and is enriched for the heritability of complex traits and diseases in humans. Our results highlight the importance of cross-species functional comparison in illustrating the genetic and evolutionary basis of complex phenotypes.
Transcriptional maintenance of cortical somatostatin interneuron subtype identity during migration
Authors: Hermany Munguba, Kasra Nikouei, Hannah Hochgerner, Polina Oberst, Alexandra Kouznetsova, Jesper Ryge, Ana Belén Muñoz-Manchado, Jennie Close, Renata Batista-Brito, Sten Linnarsson, Jens Hjerling-Leffler
Journal: Neuron (2023)